Periodic Reporting for period 1 - RESPVR (Investigating the sensorimotor mechanisms of respiration and their contribution to bodily self-consciousness by combining virtual reality, physiology, and neuroimaging.)
Okres sprawozdawczy: 2020-11-01 do 2022-10-31
Breathing-related manipulations modulate the bodily self-consciousness. Such effects are particularly reliable and robust for breathing agency that is the feeling of controlling the act of breathing. Interestingly, breathing control is very similar to the control of action. This project approaches breathing and breathing function in a novel theoretical and experimental framework, providing firm behavioural and neural evidence to link sensorimotor processes of breathing to sensorimotor aspects of bodily self-consciousness, especially breathing agency. The aim of the research proposed here is, first, to scientifically advance our understanding of human respiration by validating a novel paradigm in healthy subjects, by combining the use of virtual reality (VR), online physiology and cutting-edge neuroimaging techniques. Subsequently, such new methods and findings will be applied to patients suffering from Hyperventilation Syndrome (HVS, i.e. abnormal breathing patterns in the absence of an organic respiratory disease) to gain unprecedented insights into HVS underlying mechanisms. Finally, in line with the public health strategies proposed by Europe 2020, the project findings will increase science-based understanding of HVS and will inform the development of future VR-based rehabilitation in respiration disorders.
Study 1: We created a novel visuo-respiratory agency paradigm, using VR, to allow the systematic investigation of the sensorimotor control of breathing and its accompanying sense of agency. Participants (n=36) were embodied in a 3-D virtual avatar breathing either in synchrony (no-delay condition) or with an additional normalized delay (varying from 1/8 to 9/8 of their breathing cycle duration). Motor adaptation as well as agency ratings over the avatar’s breathing movement were analysed using robust statistics. Breathing sense of agency was maximal in the no-delay and full-delay conditions, and minimal in the half-delay condition. Moreover, when self-attributing the breathing movement, participants automatically adapted their breathing to the delayed visual feedback, in an optimal manner. Our novel findings extend the sense of agency literature to respiration and show a clear relationship between breathing automatic sensorimotor processes and conscious breathing sense of agency.
Study 2: Our novel paradigm - with limited movement - was combined and piloted with neuroimaging using a unique MRI-compatible VR system, offering the unprecedented opportunity to precisely identify the networks underlying breathing and its sense of agency, and their dynamics, using fMRI. A pilot of 17 subjects was first ran leading to interesting preliminary results. Previous behavioral results from Study 1 were reproduced, showing that sense of agency depends on the temporal delay of the visual feedback, and that motor adaptation depends on the temporal delay only when the subject self-attributes the movement. Our preliminary main result was that agency judgments were related to activations in the insula, the supramarginal gyrus, the middle frontal gyrus, the cingulate cortex, the inferior parietal lobule, the cerebellum, and the pre-central gyrus. Additionally, we observed that motor adaptation was linked to activations in the insula, the supramarginal gyrus, the pre-supplementary motor area, the cerebellum, and the precentral gyrus. These results resemble those obtained when investigating upper limb movements’ agency. This suggests that a similar process underlies upper limb movements ‘and breathing agency. Due to delays induced by the pandemic, the final sample (n=39) is still being analyzed.
Study 3: Following the validation of the paradigm and the determination of the behavioural and neural mechanisms in healthy subjects, we applied its behavioural version (Study 1) to patients suffering from HVS, to gain insights in HVS underlying mechanisms by comparing breathing motor adaptation and breathing agency in patients and age-matched healthy participants. We managed to recruit 14 HVS patients from the Pneumology ward of the Geneva Hospitals and recruited 14 perfectly matched control in terms of age and gender. Due to delays induced by the pandemic, the analyses are still ongoing.
Dissemination & Exploitation:
The strategy to disseminate was composed of two parts. (1) The results were disseminated within the LNCO, EPFL, and Campus Biotech during the events such as internal LNCO lab meetings and Project Presentation Seminars of Campus Biotech; (2) The results were also disseminated to the broad scientific community. Preliminary and results were presented in international research meetings such as meetings led by the Association for the Scientific Study of Consciousness (poster), the European Respiratory Society (poster and talk), and the Dyspnea Society (poster and talk). I also presented my data to my former laboratory at the Brighton and Sussex medical School (Brighton, UK) and was invited to give a talk as a keynote speaker in a symposium at the IEEE International Conference on Development and Learning 2022, in London.
Regarding publications, a comprehensive review on the topics of this project has been published in Biological psychology and a derived clinical application of this project is under review in European Respiratory Journal Open Research. Three more manuscripts remain under preparation and will be soon submitted. All original research manuscripts are/will be registered as pre-print on bioRxiv to ensure open science (https://www.biorxiv.org/(odnośnik otworzy się w nowym oknie)). Finally, all my publications and conference talks were shared on my ResearchGate, Twitter, and LinkedIn profiles as well as on the LNCO website. The funding source, as well as the reference number of the grant, are specified in all publications.
Present findings were as a basis to write a grant proposal for the French ATIP Avenir CNRS/INSERM 2022 program. Such grant was selected by the jury.
Study 2: Our novel paradigm - with limited movement - was combined and piloted with neuroimaging using a unique MRI-compatible VR system, offering the unprecedented opportunity to precisely identify the networks underlying breathing and its sense of agency, and their dynamics, using fMRI. A pilot of 17 subjects was first ran leading to interesting preliminary results. Previous behavioral results from Study 1 were reproduced, showing that sense of agency depends on the temporal delay of the visual feedback, and that motor adaptation depends on the temporal delay only when the subject self-attributes the movement. Our preliminary main result was that agency judgments were related to activations in the insula, the supramarginal gyrus, the middle frontal gyrus, the cingulate cortex, the inferior parietal lobule, the cerebellum, and the pre-central gyrus. Additionally, we observed that motor adaptation was linked to activations in the insula, the supramarginal gyrus, the pre-supplementary motor area, the cerebellum, and the precentral gyrus. These results resemble those obtained when investigating upper limb movements’ agency. This suggests that a similar process underlies upper limb movements ‘and breathing agency. Due to delays induced by the pandemic, the final sample (n=39) is still being analyzed.
Study 3: Following the validation of the paradigm and the determination of the behavioural and neural mechanisms in healthy subjects, we applied its behavioural version (Study 1) to patients suffering from HVS, to gain insights in HVS underlying mechanisms by comparing breathing motor adaptation and breathing agency in patients and age-matched healthy participants. We managed to recruit 14 HVS patients from the Pneumology ward of the Geneva Hospitals and recruited 14 perfectly matched control in terms of age and gender. Due to delays induced by the pandemic, the analyses are still ongoing.
Dissemination & Exploitation:
The strategy to disseminate was composed of two parts. (1) The results were disseminated within the LNCO, EPFL, and Campus Biotech during the events such as internal LNCO lab meetings and Project Presentation Seminars of Campus Biotech; (2) The results were also disseminated to the broad scientific community. Preliminary and results were presented in international research meetings such as meetings led by the Association for the Scientific Study of Consciousness (poster), the European Respiratory Society (poster and talk), and the Dyspnea Society (poster and talk). I also presented my data to my former laboratory at the Brighton and Sussex medical School (Brighton, UK) and was invited to give a talk as a keynote speaker in a symposium at the IEEE International Conference on Development and Learning 2022, in London.
Regarding publications, a comprehensive review on the topics of this project has been published in Biological psychology and a derived clinical application of this project is under review in European Respiratory Journal Open Research. Three more manuscripts remain under preparation and will be soon submitted. All original research manuscripts are/will be registered as pre-print on bioRxiv to ensure open science (https://www.biorxiv.org/(odnośnik otworzy się w nowym oknie)). Finally, all my publications and conference talks were shared on my ResearchGate, Twitter, and LinkedIn profiles as well as on the LNCO website. The funding source, as well as the reference number of the grant, are specified in all publications.
Present findings were as a basis to write a grant proposal for the French ATIP Avenir CNRS/INSERM 2022 program. Such grant was selected by the jury.
Our findings show that it is possible to experience sense of agency over breathing and that the computational theory of motor control can be applied to such breathing movements, as observed for upper-limb movements. We also highlighted a clear relationship between breathing automatic sensorimotor processes (i.e. breathing motor adaptation) and conscious breathing sense of agency. Moreover, our preliminary fMRI data suggest that brain areas involved in breathing agency are similar to the network activated during agency over upper limb movements. Our work is novel as it extends the vast literature on the sense of agency to respiration, by suggesting that breathing can be considered as any other and can be modulated by the simple use of visual feedback. Such line of research is bearing important implications for fundamental research and is informing the development of smart and individualized VR-based respiratory rehabilitation tools.